. The objectives of this proposal will be to develop synthetic approaches to classes of compounds which exhibit anti-HIV activity and to prepare derivatives which might be used for mechanism of action and structure-activity studies. Part I of this proposal is focussed on the synthesis of pradimicin A, a natural product which has activity against the HIV virus and also against organisms which are responsible for opportunistic infections in AIDS victims. Pradimicin A is a disaccharide of a nonlinear aromatic polyketide. The goals of this application, therefore, will be (1) to develop methods for the synthesis of nonlinear polycyclic aromatic systems, (2) to prepare representative antibiotics of the nonlinear polycyclic aromatic class, (3) to prepare and test structural analogs of pradmicin for anti-HIV activity and (4) to prepare labelled derivatives of pradimicin A for use in studies directed at identification of the pradimicin binding sites. Part II of the proposal deals with the efficient synthesis of TIBO antibiotics. The goals of this part of the proposal are (1) to develop a route which makes compounds of this class readily available for testing and (2) to develop a structure-activity correlation. In addition, radiolabelled compounds will be prepared for use in mechanism of action studies.